Cambridge Healthtech Institute’s Fifth Annual
Rapid Methods to Assess Quality & Stability of Biologics:
Improving Prediction and Screening
Part of CHI's Ninth Annual The Bioprocessing Summit
August 21-22, 2017 | Westin Copley Place | Boston, MA
Assurance of quality and stability of biologic formulations over the course of intended usage is critical in developing safe and efficacious biopharmaceutical products. Increasing regulatory expectations and aggressive development timelines calls for
rapid methodologies to predict and assess the quality and stability of biologics. The fifth annual Rapid Methods to Assess Quality & Stability of Biologics conference brings together experts in analytical and formulation development to discuss
regulatory expectations, prediction and manipulation for protein stability and instabilities caused by particles, higher order structures and impurities. Conference will provide platform to share case studies, unpublished and innovative work on methods
employed in real time and accelerated stability studies, protein aggregates and effective use of DoE for assessment and data comparability from early to late stage development.
Monday, August 21
8:00 am Short Course Registration Open
9:00 – 11:30 Recommended
Morning Short Courses*
SC4: Accelerated Stability Testing of Biologics
* Separate registration required
11:30 Main Conference Registration Open
1:00 pm Chairperson’s Opening Remarks
Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering, University of Delaware
1:10 KEYNOTE PRESENTATION:
Developing Competitive Biologics Products Necessitates Combining Formulation Design, Process Development, and Device Integration
Yatin Gokarn, Ph.D., Head, Global Pharmaceutical Development Biologics, Sanofi
There is a increasing need for designing and developing competitive biologics drug products in today’s biotherapeutics marketplace when many new modalities and new product formats are making their way to market and many promising leads continue
to fill the research and development pipelines. A competitive patient-centric product necessitates a holistic product development strategy that takes into consideration formulation design, process development, analytics and device integration.
1:45 How Well Can We Predict Protein-Protein Interactions and Aggregation Propensity Using Molecular Models during Candidate and Formulation Assessment?
Christopher J. Roberts, Ph.D., Professor, Chemical & Biomolecular Engineering,
University of Delaware
The presentation will focus on approaches for identifying aggregation-prone proteins and formulation conditions based on different structural models and molecular simulation, compared to experimental results for protein-protein interactions and aggregation
rates. Examples will include monoclonal antibodies and globular proteins at low and high concentrations, with a view to both candidate selection and formulation development.
2:15 Divide and Conquer: Comparison of Statistical and Probabilistic Tools for Risk Assessment in Multi-Stage Processes
Olga Yee, Ph.D., Principal Scientist, Drug Product Science and Technology, Bristol-Myers Squibb
Faster decisions imply acceptance of risks associated with accelerated development of compounds. In this presentation, a risk of success for a drug to meet a specification limit is quantified for a three-stage process using three approaches: worst-case
scenario, variance transmission model, and the novel approach of “divide and conquer.” A case study for a biologic drug product lifecycle from drug substance to final delivery is presented.
2:45 Refreshment Break
3:15 Connecting Prescreening Studies to Commercial Product Stability and Integrity
Mark Brader, Ph.D., Research Fellow, Moderna Therapeutics
Evaluating conformational and colloidal stability represents distinct aspects in the development of scalable bioproducts. An effective early development program will incorporate a diverse set of screening methodologies to evaluate drug candidates and
their responses to solution conditions. Traditional and emerging approaches to the accelerated prediction of long term product stability will be reviewed and a perspective presented on leveraging biophysical methods to more effectively support comparability
and biosimilarity assessments.
3:45 High Throughput, Low Volume
Subvisible Particle Screening
Bernardo Cordovez, Ph.D., President, Halo Labs
Halo labs will present a subvisible particle screening tool, the HORIZON, with detailed explanation of its Backgrounded Membrane Imaging (BMI) technology. A comparative analysis between HORIZON and flow imaging will be presented and key performance indicators
including sample volume, throughput, dynamic range, instrument repeatability will be evaluated.
4:00 Approaches to Extractables/Leachables
for Single Use Systems: Case Studies Using a Risk-based Approach
Sandi Schaible, Director, Analytical Chemistry, WuXi AppTec
There are a number of approaches when it comes to Extractables/Leachables testing for Single Use Systems in bio manufacturing. We will discuss taking a customized approach based on the risk of each component in your system.
4:30 Breakout Discussions
This session provides the opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations
or commiserate about persistent challenges. Then continue the discussion as you head into the lively exhibit hall for information about the latest technologies.
Topic: Biologics Formulation and Stability
Moderator: Haresh T. More, Ph.D., Research Investigator I, Parenteral Science and Technology, Bristol-Myers Squibb
- Current Formulation development in biologics, protein and peptides
- High Concentration Protein Formulation
- High Throughput methods, new technologies in protein biophysical assessment
Topic: Management of DP temperature excursions during shipping and in clinic
Moderator: Tatiana Nanda, Ph.D., Biopharm Product Development Investigator, Biopharm Product Sciences, GlaxoSmithKline
- Ways to allocate the allowable temperature excursion perids
- Ways for self-management of temperature excursions in clinic
Topic: Use of a platform formulation versus innovative formulation approaches for accelerated development
Moderator: Radhakrishna Maroju, Ph.D., Senior Scientist, Biologics CMC, Teva Biopharmaceuticals USA
- Risk-based analysis in the decision process.
- Unique formulation challenges for novel biologic modalities
- QbD applications in development of drug products – formulation to container closure selection
Topic: New Tools for Characterization of Protein Aggregation and Stability
Moderator: Sanket Patke, Ph.D., Research Investigator, Drug Product Science and Technology, Pharmaceutical Development, Bristol-Myers Squibb
- Novel high-throughput tools
- Strategies to detect and manage chemical degradation
- PAT for in process/ in line detection
5:30 Grand Opening Reception in the Exhibit Hall with Poster Viewing
7:00 End of Day
Tuesday, August 22
7:30 am Registration Open and Morning Coffee
7:55 Chairperson’s Remarks
Sandi Schaible, Director, Analytical Chemistry, WuXi AppTec
8:00 High Throughput Sialic Acid Analysis
Yimin Hua, Ph.D., Scientist II, Global Manufacturing Science and Technology - Analytical Science and Technology, Sanofi
The level of sialic acid is a critical quality attribute for therapeutic proteins. The level of sialic acid can be measured through glycan profiling which typically involves lengthy sample preparation procedure and challenges in separation of various
glycans. This presentation will talk about a high throughput method with simple procedure for the determination of sialic acid level in glycoproteins. This method is not only QC user friendly, but also can be used for fast screening in product and
8:30 Rapid Minor Variants Identification in Therapeutic Antibodies by an Automatic Off-Line 2D-LC/Q Exactive® System
Jin Li, Ph.D., Senior Research Associate, Analytical Development and Quality Control, Genentech, Inc.
Understanding the chemical nature of minor variants in therapeutic proteins is critical for process development and product quality control. The current techniques for minor variant characterization typically require manual fractionation to enrich the
low abundance species followed by desalting procedures to make the sample MS compatible. Herein we developed a rapid and automatic off-line 2D-LC/Q Exactive® MS workflow for mass analysis of the minor variants in a therapeutic antibody.
9:00 High-Throughput Analytics from RoboColumn Purification to Product Quality Screening
Hardip Gopani, Development Associate III, Analytical and Pharmaceutical Sciences, ImmunoGen, Inc.
With the increased use of automation in cell line screening and small scale upstream process development, demand for high-throughput analytics continues to grow. The right assay platforms and strategic choice of product quality to screen enabled us
to meet these needs. We will share our experience with setting up an automated RoboColumn purification platform for the testing of antibody harvest cell culture fluid (HCCF) samples.
Light Scattering Tools for Characterizing and Formulating Macromolecules and Nanoparticles
Julia Deuel, Applications Scientist, Wyatt Technology
From aggregates to conjugates, peptides to polysaccharides, light scattering detectors provide a comprehensive suite of biophysical characterization tools. The light scattering toolkit determines molar mass, size, charge, interactions, and conjugation
of macromolecules and nanoparticles. This seminar presents an overview of the instrumentation and example applications, focusing on µSEC-MALS-DLS, and HT-DLS.
9:45 Coffee Break in the Exhibit Hall with Poster Viewing
10:30 Novel Approach towards the Evaluation of Critical Quality Attributes and Stability of Proteins
Belinda Pastrana, Ph.D., Full Professor, Department of Chemistry, University of Puerto
Rico, Mayaguez Campus
Therapeutic proteins are highly complex molecules; their CQAs require diverse bioanalytical techniques to comply with reporting requirements to regulatory agencies. Ideally a multivariate analysis would also be needed to address stability, yet
even under the current state of technology, including proteomic and high resolution, techniques can be costly and time consuming. We have developed a DOE, label free method using Best-in-Class platform technology to aid in addressing this
11:00 Rapid Method for Total Protein Measurement Using SoloVPE Technology – Challenges and Solutions
Hsin-I Peng, Ph.D., Associate Manager, Quality Control, Regeneron Pharmaceuticals, Inc.
SoloVPE technology presents a unique platform for protein concentration measurement with key benefits including “no dilution” and “rapid reading.” When exploiting SoloVPE, protein concentration under-estimation is experienced
for highly concentrated samples, posing challenges for accurate protein concentration measurement. Our studies show standard curve data collected outside the Beer’s law linear region can unfavorably result in protein under-estimation.
Challenges and solutions when using SoloVPE technology for protein measurement will be discussed.
11:30 Punch up Biologic Development with ΔG and the HUNK
Greg Manley, Ph.D., Senior Applications Scientist, Unchained Labs
Developing biologics requires identifying an ideal construct followed by assessing a wide range of formulation space to ensure stability and minimize aggregate. Assessing ΔG is a powerful approach for the quantitative assessment of conformational
stability and aggregation. The HUNK automates the tedious and manual task of determining ΔG, allowing for quantitative stability assessment throughout biologic development. We'll discuss how HUNK can be used in conjunction with more
traditional approaches to assessing stability and aggregation propensity.
12:00 pm High Throughput Methods to Assess Stability of Biologics During Pre-Formulation and Formulation Development
Smita Raghava, Ph.D., Senior Scientist, Sterile Formulation Sciences, Merck
There is a growing demand in the pharmaceutical industry for developing orthogonal tools to accurately, rapidly, and reproducibly predict protein solution stability behaviors using limited material to improve formulation screening and manufacturability
assessment. This presentation will focus on combination of high-throughput technologies and assays for formulation and drug product development of biologics, such as monoclonal antibodies (mAbs) and mAb-based modalities. The overview of tools,
their novel implementation, and relationship to commonly conducted “stability studies” will be further discussed using examples of high-throughput workflows, pre-formulation screening, and formulation development/optimization.
12:30 Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own
1:15 Dessert Refreshment Break in the Exhibit Hall with Poster Viewing
1:55 Chairperson’s Remarks
Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly and Company
2:00 Critical Considerations in the Characterization of Protein Higher Order Structure (HOS) and Its Relationship with Stability and Function
Haripada Maity, Ph.D., Research Advisor, Formulation Development, CMC Development, Eli Lilly
Higher order structure (HOS) of a protein can be altered due to both physical and chemical instabilities. Characterization of HOS is important in assessing comparability, formulation and process development. This presentation will discuss the
(i) selection of techniques in characterization of HOS, (ii) quantitative and qualitative evaluation of characterization parameters and their sensitivity and precision, and (iii) the effect of chemical “mutagenesis” on HOS, stability
and functional properties.
2:30 Selected Poster Presentation: Challenges in Characterization of Bioprocesses and Products using Raman spectroscopy
Nobel Vale, Research Investigator II, Drug Science Product & Technology, Bristol-Myers Squibb Company
Raman spectroscopy is a viable spectroscopic tool to analyze biological samples. Raman’s spectral specificity for molecules, insensitivity to water and ability to analyze without sample manipulation are attractive features. In this presentation
challenges for two different real-time Raman applications. In one example the effect of fluorescence background, cells/debris, and spectral interference on spectra during in-situ cell culture monitoring is discussed. In another example challenges
for characterization of intact protein solutions are presented.
3:00 Selected Poster Presentation: Higher Order Structural View Of The Effects Of Oxidation On The Structure, Stability, And Aggregation Of Interferon Alpha-2a
Dinen D. Shah, Ph.D Candidate, Department of Pharmaceutical Sciences, University of Colorado
Oxidation of therapeutic proteins during their formulation and shelf-life is a persistent challenge facing the biopharma industry. We used IFN-αlpha 2a to obtain a mechanistic understanding of how oxidation affects its structure, stability,
aggregation and function. Using high resolution techniques such as 2D NMR helped us to pinpoint the residue level structural changes that correlate with functional changes.
3:30 Refreshment Break in the Exhibit Hall with Poster Viewing
4:15 Using Endoglycosidase and High Resolution Mass Spectrometry to Estimate the Level of MAN-5 and Afucosylation in Monoclonal Antibodies
Ming-Ching Hsieh, Ph.D., Research Advisor, BioAnalytical Science, Eli Lilly and Company
This presentation will discuss a rapid glycosylation analysis using fast fluorescent labeling for overall glycan profiles and endoglycosidases with site specific protease for estimation of MAN-5 glycan and afucosylation levels in biologics.
4:45 Understanding & Verifying Flow Imaging Particle Counters
Dean Ripple, Ph.D., Leader, Bioprocess Measurements Group, National Institute of Standards and
Flow imaging instruments can measure particles in biotherapeutics with potentially greater accuracy than light obscuration. However, verification methods for flow imaging instruments are not yet standardized. I will present methods used to
verify the performance of flow imaging particle counters. Topics will include the use of reference materials, examination of data self-consistency, and solutions to common problems. Methods to understand errors in counts and reported size
will also be presented.
5:15 Close of Conference
6:00 – 8:30 Recommended
Dinner Short Course*
SC8: Protein Aggregation: Mechanism, Characterization and Consequences
* Separate registration required